An Expert Report on WDB-178: A Preclinical Investigational Agent Targeting KRAS G12C

1. Executive Summary

WDB-178 is an investigational therapeutic agent in the preclinical phase of development, originated by Revolution Medicines, Inc..[1] It is classified as a non-degrading molecular glue and is designed to target the oncogenic KRAS G12C protein, a well-validated driver in various human cancers. The mechanism of action of WDB-178 is understood to be as a KRAS G12C inhibitor, operating through Revolution Medicines' proprietary tri-complex inhibitor platform.[2] This platform distinctively targets the active, GTP-bound conformation of RAS proteins, commonly referred to as RAS(ON). The therapeutic strategy involves inducing the formation of a ternary complex comprising WDB-178, an intracellular chaperone protein (such as cyclophilin A), and the RAS(ON) target protein. This tri-complex formation is intended to sterically hinder the interaction of KRAS G12C(ON) with its downstream effector proteins, thereby abrogating oncogenic signaling pathways.[4]

Given its target, WDB-178 holds therapeutic potential for a range of neoplasms characterized by KRAS G12C mutations.[1] The novel approach of targeting KRAS(ON) may confer advantages over existing KRAS G12C inhibitors that primarily bind the inactive GDP-bound (OFF) state, particularly in the context of overcoming intrinsic or acquired resistance mechanisms.[9] WDB-178 represents a next-generation strategy in KRAS G12C inhibition, leveraging a scientifically validated platform technology aimed at drugging the active, oncogenic form of RAS. This approach addresses a significant unmet medical need in the landscape of KRAS-mutant cancers, where existing therapies face limitations. The classification of WDB-178 as a "non-degrading molecular glue" [1] and its development by Revolution Medicines, a company with a strong portfolio of RAS(ON) tri-complex inhibitors [2], strongly suggests a mechanism distinct from simple protein degradation and aligns with the company's focus on inhibiting the active RAS state.[2]

2. Introduction to WDB-178

2.1. Identification

The investigational compound is designated as WDB-178, with WDB178 also listed as a synonym.[1]

2.2. Drug Class

WDB-178 is categorized as a "non-degrading molecular glue".[1] Molecular glues are small molecules that function by inducing or stabilizing protein-protein interactions (PPIs).[14] Unlike degradative molecular glues (e.g., certain immunomodulatory imide drugs or PROTACs – Proteolysis Targeting Chimeras) that typically recruit E3 ubiquitin ligases to tag the target protein for proteasomal degradation, non-degrading molecular glues modulate the target protein's function, conformation, or interactions with other proteins without causing its degradation.[14] This distinction is critical as it implies a different pharmacological outcome and potentially different pharmacokinetic/pharmacodynamic (PK/PD) profiles and off-target considerations compared to protein degraders.

2.3. Developer: Revolution Medicines, Inc.

WDB-178 is being developed by Revolution Medicines, Inc., a clinical-stage precision oncology company.[2] The company's primary focus is on the development of novel targeted therapies for RAS-addicted cancers, with significant emphasis on inhibiting elusive frontier targets within the RAS and mTOR signaling pathways.[2] A cornerstone of Revolution Medicines' approach is its "Tri-Complex Inhibitor Platform." This platform is specifically engineered to target the active, GTP-bound state of RAS proteins (RAS(ON)), which has historically been challenging to drug.[2]

Revolution Medicines has a pipeline of RAS(ON) inhibitors, including daraxonrasib (RMC-6236, a RAS(ON) multi-selective inhibitor), elironrasib (RMC-6291, a RAS(ON) G12C-selective inhibitor), and zoldonrasib (RMC-9805, a RAS(ON) G12D-selective inhibitor), which are currently in clinical development.[2] The established expertise and the progression of these related compounds through preclinical and clinical development provide a robust scientific foundation and a degree of validation for the therapeutic strategy likely employed by WDB-178. The consistent focus on RAS(ON) targets and the application of the tri-complex mechanism across their pipeline strongly suggest that WDB-178, as a KRAS G12C inhibitor from this company, leverages this well-characterized and innovative platform.[2]

3. The Oncogenic Target: KRAS G12C

3.1. KRAS Mutations in Cancer

The KRAS gene, a member of the RAS superfamily of small GTPases, is one of the most frequently mutated oncogenes in human cancers, playing a critical role in tumor initiation, progression, and maintenance.[8] RAS proteins, including KRAS, function as molecular switches, cycling between an inactive GDP-bound (OFF) state and an active GTP-bound (ON) state.[12] In the ON state, KRAS interacts with various downstream effector proteins (e.g., RAF kinases, PI3-kinases) to activate signaling pathways that regulate cell proliferation, survival, and differentiation.[13]

Oncogenic mutations in KRAS, such as the G12C substitution (glycine to cysteine at codon 12), impair the intrinsic GTPase activity of the KRAS protein and/or render it insensitive to GTPase-activating proteins (GAPs). This results in a constitutive accumulation of KRAS in the active GTP-bound state, leading to aberrant and continuous downstream signaling that drives uncontrolled cell growth and malignant transformation.[8]

3.2. KRAS G12C as a Therapeutic Target

The KRAS G12C mutation is particularly prevalent in certain cancer types, most notably in approximately 13-15% of non-small cell lung cancers (NSCLC), 3-5% of colorectal cancers (CRC), and a smaller fraction of pancreatic and other solid tumors.[8] For decades, KRAS was considered "undruggable" due to its high affinity for GTP (picomolar range) and the smooth, featureless protein surface in its active state, which lacked obvious pockets for small molecule binding.[3]

3.3. First-Generation KRAS G12C Inhibitors

Recent advancements in drug discovery have led to a paradigm shift with the development and FDA approval of covalent inhibitors specifically targeting the mutant cysteine residue in KRAS G12C, such as sotorasib and adagrasib.[3] These first-generation inhibitors function by binding to and trapping KRAS G12C in its inactive, GDP-bound (OFF) state, thereby preventing its activation and subsequent signaling.[7]

While these KRAS(OFF) inhibitors have demonstrated clinically meaningful activity and represent a significant therapeutic advance, their efficacy is not universal. A substantial proportion of patients do not respond, and among initial responders, acquired resistance frequently emerges, limiting the durability of clinical benefit.[3] Mechanisms of resistance can include secondary KRAS mutations, alterations in upstream or downstream signaling pathway components, or histologic transformation.[12] The development of resistance to KRAS(OFF) inhibitors underscores the unmet medical need for novel therapeutic strategies with distinct mechanisms of action. Targeting the active KRAS(ON) state, as WDB-178 is designed to do, represents one such innovative approach to potentially overcome these limitations.

4. WDB-178: Mechanism of Action and Preclinical Rationale

4.1. Target Engagement

WDB-178 is an inhibitor specifically targeting the KRAS G12C mutant protein.[1]

4.2. Non-Degrading Molecular Glue Mechanism

The compound is classified as a "non-degrading molecular glue".[1] This designation implies that WDB-178 functions by inducing or stabilizing a protein-protein interaction involving KRAS G12C, which ultimately leads to the inhibition of its oncogenic function without causing its proteasomal degradation.[14] This non-degradative mode of action contrasts with that of PROTACs or other degradative molecular glues, which aim to eliminate the target protein. The pharmacological consequence of non-degradation may include differences in the duration of action, potential for off-target effects related to the ubiquitin-proteasome system, and distinct resistance profiles.

4.3. Revolution Medicines' Tri-Complex Inhibitor Platform

The specific mechanism of WDB-178 is understood through the lens of Revolution Medicines' validated "Tri-Complex Inhibitor Platform," which targets the active RAS(ON) state.[2]

• Core Concept: These inhibitors are small molecules designed to first bind to an abundant intracellular chaperone protein, typically cyclophilin A (CypA), forming a binary complex (e.g., WDB-178:CypA). This initial binding event is crucial as it remodels the surface of the drug-chaperone complex, creating a "neomorphic" binding interface. This newly formed interface possesses high affinity and selectivity for the target RAS(ON) protein.[2]
• Mechanism of Inhibition: The drug:CypA binary complex then engages the active, GTP-bound KRAS G12C, forming a stable ternary "tri-complex" (e.g., WDB-178:CypA:KRASG12C(ON)). The formation of this tri-complex sterically hinders the ability of KRASG12C(ON) to interact with its downstream effector proteins, such as RAF kinases and PI3-kinases. This blockade of effector binding effectively abrogates the oncogenic signaling cascades driven by the mutant KRAS protein.[4]
• Targeting Active KRAS(ON): A fundamental and distinguishing feature of this platform is its ability to directly target KRAS in its active, GTP-bound (ON) conformation. This is significant because the ON state is the form of RAS that actively drives oncogenic signaling and cell proliferation.[2] By inhibiting RAS(ON), these compounds aim to shut down the aberrant signaling at its source.
• Covalent Interaction Potential: While the general tri-complex platform can utilize both covalent and non-covalent interactions with the RAS target, inhibitors targeting the G12C mutation often employ a covalent mechanism by forming a bond with the mutant cysteine residue. Elironrasib (RMC-6291), a clinical-stage KRASG12C(ON) inhibitor from Revolution Medicines, utilizes such a covalent interaction.[4] Given that WDB-178 also targets KRAS G12C, a similar covalent binding mode is plausible, though not explicitly confirmed for WDB-178 in the available information.
• Supporting Evidence from Platform Analogues: The mechanism of tri-complex formation and RAS(ON) inhibition has been detailed in scientific publications from Revolution Medicines. A 2023 publication in Science by Schulze et al. described this approach for the KRASG12C(ON) tool inhibitor RMC-4998 and the clinical candidate elironrasib (RMC-6291), highlighting the role of CypA in mediating selective binding to active KRASG12C.[4] Further elaboration on the discovery of elironrasib using this platform was published in the Journal of Medicinal Chemistry in 2025.[8]

The non-degrading nature of WDB-178, functioning via steric blockade of effector binding as part of a tri-complex, offers a distinct pharmacological approach compared to inhibitors that induce target degradation or those that only bind the inactive KRAS(OFF) state. This could translate to a different spectrum of efficacy, resistance mechanisms, and safety considerations.

4.4. Comparison of RAS Inhibitor Mechanisms

The development of RAS(ON) inhibitors like WDB-178 addresses the limitations observed with first-generation KRAS(OFF) inhibitors. The table below contrasts these mechanisms:

Feature	KRAS(OFF) Inhibitors (e.g., Sotorasib, Adagrasib)	RAS(ON) Tri-Complex Inhibitors (e.g., WDB-178, Elironrasib)
Target RAS State	Inactive, GDP-bound (OFF) state 7	Active, GTP-bound (ON) state 2
Mechanism of Action	Covalent binding to G12C, trapping KRAS in OFF state 3	Forms a tri-complex with a chaperone protein (e.g., CypA) and KRAS(ON), sterically blocking effector interactions 4
Involvement of Chaperone	No	Yes (e.g., Cyclophilin A) 2
Primary Mode of Inhibition	Covalent trapping of inactive state 3	Steric blockade of active state signaling (may be covalent for G12C variants like elironrasib) 4
Target Degradation	No	No (non-degrading molecular glue) 1
Known Resistance Addressed	Aims to overcome resistance due to KRAS remaining in or reverting to ON state; targets the continuously signaling form 5	Potentially overcomes resistance mechanisms that reactivate RAS signaling or bypass KRAS(OFF) inhibition 5

This comparative framework underscores the distinct approach of WDB-178 and its platform, aiming to inhibit the direct driver of oncogenic signaling, the KRAS(ON) protein.

5. Preclinical Evidence and Profile of WDB-178 (and Related Platform Compounds)

5.1. Direct Preclinical Data for WDB-178

Specific in vitro or in vivo efficacy, pharmacokinetic (PK), pharmacodynamic (PD), or detailed safety data for WDB-178 itself are not extensively available in the public domain through the provided research materials, beyond its classification as a preclinical compound targeting KRAS G12C.[1] The Synapse platform indicates the existence of proprietary data ("100 Clinical Results associated with WDB-178. Login to view more data"), but this is not accessible.[1] This lack of detailed public information is characteristic of compounds in the early stages of preclinical development, where data is often disclosed progressively at scientific conferences or in publications as development milestones are reached.

5.2. Inferred Preclinical Profile from Revolution Medicines' RAS(ON) Tri-Complex Platform and Analogues

Given the shared platform technology and target class, the preclinical profile of WDB-178 can be inferred from data reported for analogous RAS(ON) tri-complex inhibitors developed by Revolution Medicines, notably elironrasib (RMC-6291, a KRASG12C(ON)-selective inhibitor) and related tool compounds like RMC-4998 and RMC-7977.

• Potent In Vitro Inhibition of KRASG12C(ON): Elironrasib (RMC-6291) has demonstrated potent inhibition of KRASG12C(ON) signaling in cellular assays, with a reported median IC50​ of 0.11 nM in KRASG12C mutant cells.5 These inhibitors achieve their effect by sterically blocking the interaction of KRASG12C(ON) with its downstream effectors, leading to the inhibition of critical signaling pathways such as the ERK pathway, and ultimately inducing apoptosis in KRASG12C-mutant cancer cells.5
• In Vivo Tumor Regression: Compounds from the tri-complex inhibitor platform have consistently shown robust anti-tumor activity in vivo. Preclinical studies using xenograft models of KRASG12C mutant human cancers have reported significant tumor regressions following treatment with these RAS(ON) inhibitors.4 For instance, RMC-7977, a preclinical tool compound representative of the multi-RAS(ON) inhibitor daraxonrasib (RMC-6236), exhibited durable anti-tumor activity in KRAS-mutated NSCLC models.10 Moreover, the combination of RMC-7977 with RMC-4998 (a preclinical tool compound for elironrasib) not only enhanced anti-tumor activity but also led to cures (recurrence-free survival after treatment withdrawal) in some KRAS G12C NSCLC preclinical models.10 Elironrasib itself, when administered orally at 200mg/kg daily, significantly inhibited tumor growth and induced immunological memory in murine tumor models.5
• Overcoming Resistance Mechanisms: A key therapeutic rationale for targeting KRAS(ON) is the potential to overcome resistance mechanisms that limit the efficacy of KRAS(OFF) inhibitors. The tri-complex platform is designed to address adaptive resistance, such as that mediated by receptor tyrosine kinase (RTK) signaling.9 Preclinical data indicate that RMC-7977 overcame acquired resistance to both RAS(OFF) and RAS(ON) G12C-selective inhibitors in advanced KRAS G12C-mutated NSCLC models.10 Furthermore, elironrasib (RMC-6291) has shown preliminary clinical activity in patients whose tumors had progressed on first-generation KRASG12C(OFF) inhibitors, providing clinical validation for this approach.5
• Pharmacokinetics (PK) and Pharmacodynamics (PD): Oral bioavailability is a desirable characteristic for oncology drugs. Elironrasib (RMC-6291) has been reported to be orally bioavailable.5 The tri-complex mechanism is designed to achieve sustained target engagement and inhibition of the RAS signaling pathway.
• Safety and Tolerability (Inferred): While specific preclinical toxicology data for WDB-178 are not available, the progression of several related compounds from Revolution Medicines' RAS(ON) platform—RMC-6236 (daraxonrasib), RMC-6291 (elironrasib), and RMC-9805 (zoldonrasib)—into clinical trials suggests that the platform generally yields compounds with an acceptable preclinical safety profile.2 Early clinical data for daraxonrasib, alone and in combination with pembrolizumab, indicated a generally manageable safety profile.18

The consistent and potent preclinical efficacy demonstrated by multiple compounds from Revolution Medicines' RAS(ON) tri-complex platform, particularly the KRAS G12C-selective inhibitor elironrasib (RMC-6291), provides a strong basis to anticipate a promising preclinical profile for WDB-178. The shared platform technology, the specific KRASG12C(ON) target, and the likely similar chemical modality (tri-complex molecular glue) make the data from elironrasib and related tool compounds highly pertinent for inferring the potential characteristics of WDB-178.

5.3. Summary of Key Preclinical Data for Revolution Medicines' KRASG12C(ON) Tri-Complex Inhibitors (Analogous to WDB-178)

Compound (Analogous to WDB-178)	Assay Type	Key Finding	Source Snippet(s)
Elironrasib (RMC-6291)	In Vitro	Median IC50​ of 0.11 nM in KRASG12C mutant cells; inhibits ERK signaling; induces apoptosis.	5
Elironrasib (RMC-6291)	In Vivo	200mg/kg p.o. qd significantly inhibits tumor growth and induces immunological memory in murine tumor models.	5
RMC-4998 (tool for RMC-6291)	In Vivo	In combination with RMC-7977, elicited cures in some KRAS G12C NSCLC preclinical models.	10
Platform (KRASG12C Inhibitors)	In Vivo	Drives tumor regressions in xenograft models; overcomes RTK-mediated escape mechanisms.	9
Platform (KRASG12C Inhibitors)	Mechanism	Forms tri-complex with CypA and KRASG12C(ON), sterically blocking effector binding.	4
Elironrasib (RMC-6291)	Clinical (Prelim.)	Shows clinical activity in patients progressed on KRASG12C(OFF) inhibitors.	5
RMC-7977 (tool for RMC-6236)	In Vivo	Overcame acquired resistance to RAS(OFF) and RAS(ON) G12C-selective inhibitors in advanced KRAS G12C-mutated NSCLC models.	10

This table consolidates the preclinical evidence from related compounds, offering a structured view of the platform's capabilities and, by extension, the anticipated profile of WDB-178.

6. Therapeutic Potential and Development Outlook

6.1. Primary Indication

WDB-178 is being developed for the treatment of neoplasms (cancers).[1] Given its specific targeting of the KRAS G12C mutation, the primary therapeutic focus will be on solid tumors known to harbor this genetic alteration. These include, but are not limited to, non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC), which are among the most common KRAS G12C-mutated malignancies.[5]

6.2. Current Development Stage

WDB-178 is currently in the preclinical phase of development.[1] This stage typically involves extensive in vitro characterization (e.g., potency, selectivity, mechanism of action studies) and in vivo studies in animal models to assess efficacy, pharmacokinetics, pharmacodynamics, and safety/toxicology.

6.3. Anticipated Next Steps in Development

Following successful completion of preclinical studies, the anticipated development pathway for WDB-178 would involve:

1. IND-Enabling Studies: Comprehensive toxicology and safety pharmacology studies conducted under Good Laboratory Practice (GLP) conditions to support the safety of administering the drug to humans.
2. Chemistry, Manufacturing, and Controls (CMC): Development and validation of the manufacturing process for WDB-178 to ensure consistent quality and scalability for clinical trial supply and potential commercialization.
3. Investigational New Drug (IND) Application: Submission of an IND application to regulatory authorities, such as the U.S. Food and Drug Administration (FDA), seeking permission to initiate human clinical trials.

The development trajectory of elironrasib (RMC-6291), another KRASG12C(ON) inhibitor from Revolution Medicines' tri-complex platform, provides a relevant precedent. Elironrasib has progressed from preclinical development into Phase 1/1b clinical trials (e.g., NCT05462717, NCT06128551, NCT06162221).[4] This progression suggests a viable path for WDB-178, assuming positive preclinical outcomes. Companies often leverage prior experience and regulatory interactions from platform-derived compounds to streamline the development of subsequent candidates.

6.4. Intellectual Property

Revolution Medicines, Inc. holds patents related to WDB-178.[1] While specific patent numbers for WDB-178 are not detailed in the provided snippets, it is standard practice for biopharmaceutical companies to secure robust intellectual property (IP) protection for their novel compounds and platform technologies. These patents likely cover the chemical matter of WDB-178, its method of use in treating KRAS G12C-driven cancers, and potentially aspects of the tri-complex inhibitor platform itself. The Synapse platform indicates "100 Patents (Medical) associated with WDB-178," which, for a preclinical compound, suggests a comprehensive patenting strategy covering the broader technology and its applications.[1] A strong IP portfolio is fundamental for protecting the innovation and securing the future commercial potential of WDB-178.

7. Expert Analysis and Concluding Remarks

WDB-178 emerges from the provided information as a preclinical investigational agent with a scientifically compelling profile, primarily defined by its classification as a non-degrading molecular glue and its origin from Revolution Medicines' innovative tri-complex RAS(ON) inhibitor platform. This platform is designed to address the oncogenic KRAS G12C protein, a target of high significance in oncology.

The key differentiating factor for WDB-178 and its platform analogues is the ability to target the active, GTP-bound (ON) state of KRAS. First-generation KRAS G12C inhibitors target the inactive (OFF) state, and while they have provided clinical benefit, their efficacy is often limited by intrinsic and acquired resistance mechanisms that frequently involve the reactivation or persistence of KRAS(ON) signaling. By directly engaging KRASG12C(ON), WDB-178 has the potential to overcome these limitations and offer a more profound and durable inhibition of oncogenic signaling. The tri-complex mechanism, involving the recruitment of an intracellular chaperone like cyclophilin A to create a neomorphic binding surface on KRASG12C(ON), represents a novel chemical biology strategy. This approach may enable the drugging of targets previously considered intractable due to their surface characteristics in the active state. Furthermore, the oral bioavailability demonstrated by related compounds from this platform, such as elironrasib [5], suggests that WDB-178 may also be developed as an oral therapeutic, which would offer a significant advantage in terms of patient convenience and compliance.

Despite the promising rationale, the translation of preclinical findings to clinical success is a well-recognized challenge in drug development. The long-term safety implications of modulating chaperone proteins like CypA, and the overall tolerability of the tri-complex inhibitory approach in human subjects, will require meticulous evaluation in future clinical trials. The field of KRAS inhibition is intensely competitive, with numerous agents in development. For WDB-178 to establish a significant clinical niche, it will need to demonstrate clear advantages in terms of efficacy, safety, durability of response, or ability to overcome resistance compared to existing and emerging therapies.

If WDB-178 successfully navigates clinical development, it could represent a new therapeutic paradigm for patients with KRAS G12C-driven cancers, potentially as a monotherapy or as a crucial component of combination regimens. The robust preclinical efficacy, including tumor regressions and the overcoming of resistance, observed with analogous compounds from the Revolution Medicines platform, provides a strong foundation for the continued development of WDB-178.

Future research and disclosures will be critical. Specifically, the "non-degrading" nature of WDB-178 raises questions about the duration of target inhibition in vivo, particularly if the interaction is not covalent, and how this compares pharmacodynamically to covalent KRAS(OFF) inhibitors or to KRAS degraders. The persistent presence of a tri-complex, as opposed to target elimination by degraders, might also present a different immunogenic profile, which warrants investigation. These aspects will be important to monitor as more data on WDB-178 and related RAS(ON) inhibitors become available.

In conclusion, WDB-178 is a noteworthy preclinical candidate that embodies an advanced and scientifically rational approach to targeting the oncogenic KRAS G12C protein. Its development leverages a validated platform technology with the potential to address significant unmet needs in the treatment of KRAS-mutant cancers. The progress of WDB-178, alongside other RAS(ON) inhibitors from Revolution Medicines' pipeline, will be closely watched by the oncology community.

Works cited

1. WDB-178 - Drug Targets, Indications, Patents - Patsnap Synapse, accessed May 19, 2025, https://synapse.patsnap.com/drug/31671b3d25394996987b801646286915
2. Science – Revolution Medicines, accessed May 19, 2025, https://www.revmed.com/science/
3. Stick it to RAS: The Next Wave of Ras Therapeutics - Cytoskeleton, Inc., accessed May 19, 2025, https://www.cytoskeleton.com/december-newsletter-stick-it-to-ras-the-next-wave-of-ras-therapeutics
4. Revolution Medicines Announces Publication Describing Molecular Basis of Tri-Complex Inhibitors Targeting Oncogenic RAS(ON) Proteins, accessed May 19, 2025, https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-announces-publication-describing-molecular/
5. Elironrasib - Drug Targets, Indications, Patents - Synapse, accessed May 19, 2025, https://synapse.patsnap.com/drug/cb39e80d1a934997a778f27dc3a65f3a
6. Elironrasib (RMC-6291) | KRAS-G12C(ON) Inhibitor | MedChemExpress, accessed May 19, 2025, https://www.medchemexpress.com/rmc-6291.html
7. RMC-6291 - Drug Hunter, accessed May 19, 2025, https://drughunter.com/molecule/rmc-6291
8. Discovery of Elironrasib (RMC-6291), a Potent and Orally ..., accessed May 19, 2025, https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.4c02313
9. Revolution Medicines to Present Preclinical Data on Novel Inhibitors ..., accessed May 19, 2025, https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-present-preclinical-data-novel-inhibitors/
10. Revolution Medicines Announces Publication Demonstrating ..., accessed May 19, 2025, https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-announces-publication-demonstrating-robust/
11. Targeting KRAS - PMC - PubMed Central, accessed May 19, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC11845254/
12. Addressing KRAS Resistance, RAS(ON) Therapies Find Limelight at AACR, accessed May 19, 2025, https://www.ajmc.com/view/addressing-kras-resistance-ras-on-therapies-find-limelight-at-aacr
13. Chemical remodeling of a cellular chaperone to target the active ..., accessed May 19, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10474815/
14. Research advancements in molecular glues derived from natural product scaffolds: Chemistry, targets, and molecular mechanisms - PubMed Central, accessed May 19, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC12009069/
15. Molecular Glues Market to Register Stunning Growth During the Forecast Period (2025-2034) | DelveInsight - PR Newswire, accessed May 19, 2025, https://www.prnewswire.com/news-releases/molecular-glues-market-to-register-stunning-growth-during-the-forecast-period-20252034--delveinsight-302405373.html
16. Revolution Medicines, Inc. Common Stock (RVMD) - Nasdaq, accessed May 19, 2025, https://www.nasdaq.com/market-activity/stocks/rvmd
17. Revolution Medicines: Investor Relations, accessed May 19, 2025, https://ir.revmed.com/
18. Study of RAS(ON) Inhibitor Combinations in Patients With Advanced RAS-mutated NSCLC - LarvolClin, accessed May 19, 2025, https://clin.larvol.com/trial-detail/NCT06162221
19. Study Of RMC-6291 In Combination With RMC-6236 In Participants With Advanced KRAS G12C Mutant Solid Tumors | National Pancreatic Cancer Foundation, accessed May 19, 2025, https://www.npcf.us/clinical-trials/study-of-rmc-6291-in-combination-with-rmc-6236-in-participants-with-advanced-kras-g12c-mutant-solid-tumors/
20. Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors - ngram, accessed May 19, 2025, https://www.ngram.com/trials/NCT05462717
21. Study of RMC-6291 in Combination with RMC-6236 in Participants with Advanced KRAS G12C Mutant Solid Tumors | Clinical Research Trial Listing - CenterWatch, accessed May 19, 2025, https://www.centerwatch.com/clinical-trials/listings/NCT06128551/study-of-rmc-6291-in-combination-with-rmc-6236-in-participants-with-advanced-kras-g12c-mutant-solid-tumors?country=Italy&city=Orbassano%2520(torino)
22. accessed January 1, 1970, https://clinicaltrials.gov/study/NCT05462717
23. accessed January 1, 1970, https://clinicaltrials.gov/study/NCT06128551
24. Error | ClinicalTrials.gov, accessed May 19, 2025, https://clinicaltrials.gov/study/NCT06162221
25. accessed January 1, 1970, https://classic.clinicaltrials.gov/ct2/show/NCT05462717
26. accessed January 1, 1970, https://classic.clinicaltrials.gov/ct2/show/NCT06128551
27. accessed January 1, 1970, https://classic.clinicaltrials.gov/ct2/show/NCT06162221